The specific aims of the proposed research are to: (1) determine whether the xenobiotics butylated hydroxyanisole and 3-methylcholanthrene differentially regulate the expression of separate genes for the Yb subunit of the hepatic detoxification enzyme glutathione S-transferase in female Sprague-Dawley rats; and (2) determine the mechanism for the synergisic expression of the glutathione S-transferase Ya subunit after combined treatment of rats with butylated hydroxyanisole and 3-methylcholanthrene. Experimental results in our laboratory have shown that both the amount of activity and the amount of specific subunits for glutathione S-transferase are significantly altered by treatment of rats with these xenobiotic compounds, either singly or in combination. These results led us to hypothesize that, for the Yb subunit, each compound specifically regulate the expression of distinct forms of this subunit; and, for the Ya subunit, either each compound activates two or more separate Ya genes or the compounds act together to cause the over-expression of one Ya gene. The experiments described in this proposal are designed to test both these hypotheses. In addition to the personnel and resources available in my laboratory, the staff and equipment available in the newly established Molecular Biology Research Laboratory will be used to accomplish the stated objectives.